N-acetyl-L-cysteine is a well-known compound which is used as a therapeutic agent against chronic obstructive pulmonary diseases and chronic bronchitis. Although the first patent was filed in 1964 (GB 954268), the mechanism of action of the compound has not been established. It is also known that the corresponding disulphide of N-acetyl-L-cysteine, i.e., N,N-diacetyl-L-cystine, L-DiNAC, acts as a potent immunostimulator (SE patent application No. 9002067-8), showing an activity comparable to contemporary immunostimulants such as sodium diethyl dithiocarbamate or 2,2'-dithiobisethanol.
It has recently been found that certain salts of DiNAC with organic bases exhibit a favourable combination of non-hygroscopicity and crystallinity which permits the isolation and formulation of these salts in solid form. They have the advantages of ease of crystallisation, non-hygroscopicity and chemical stability, as well as the immunomodulating activity of DiNAC, and are thus medically useful. These salts are described in WO 93/11104.
Salts composed of an organic base and N,N-diacetylcystine (DiNAC) are generally prepared by mixing DiNAC and the organic base, as defined above, each dissolved or dispersed in a solvent or solvent mixture. Solvents, such as water, alcohols, glycols, ketones, amides, sulphoxides or other polar solvents may be used; solvent mixtures may also be used. The salt either precipitates directly from the reaction mixture, or is obtained by the addition of a less polar solvent, by evaporation, or by lyophilisation. The reaction is performed at elevated temperature or room temperature, depending on the solubility in the medium. Alternatively, the salt can be prepared by oxidation of the appropriate N-acetyl cysteine salt in an aqueous or alcoholic solution, followed by precipitation as above. The oxidation may be effected either chemically, using, e.g., hydrogen peroxide or a halogen, or electrochemically.
The above methods provide the organic salts of DiNAC in anhydrous form.